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Sökning: WFRF:(Wade T)

  • Resultat 1-10 av 83
  • [1]234567...9Nästa
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1.
  • Munn-Chernoff, M. A., et al. (författare)
  • Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies
  • 2020
  • Ingår i: Addiction Biology. - 1355-6215.
  • Tidskriftsartikel (refereegranskat)abstract
    • Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [r(g)], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from similar to 2400 to similar to 537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (r(g) = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (r(g) = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (r(g) = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (r(gs) = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.
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3.
  • Bryois, J, et al. (författare)
  • Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
  • 2020
  • Ingår i: Nature Genetics. - 1061-4036. ; 52:5, s. 482-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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4.
  • Duncan, Laramie, et al. (författare)
  • Significant Locus and Metabolic Genetic Correlations Revealed in Genome-Wide Association Study of Anorexia Nervosa
  • 2017
  • Ingår i: The American journal of psychiatry. - 1535-7228. ; 174:9, s. 850-858
  • Tidskriftsartikel (refereegranskat)abstract
    • The authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.Following uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h(2)SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.Results were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h(2)SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high-density lipoprotein cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.Anorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.
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5.
  • Wade, C. M., et al. (författare)
  • Genome Sequence, Comparative Analysis, and Population Genetics of the Domestic Horse
  • 2009
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 326:5954, s. 865-867
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We report a high-quality draft sequence of the genome of the horse ( Equus caballus). The genome is relatively repetitive but has little segmental duplication. Chromosomes appear to have undergone few historical rearrangements: 53% of equine chromosomes show conserved synteny to a single human chromosome. Equine chromosome 11 is shown to have an evolutionary new centromere devoid of centromeric satellite DNA, suggesting that centromeric function may arise before satellite repeat accumulation. Linkage disequilibrium, showing the influences of early domestication of large herds of female horses, is intermediate in length between dog and human, and there is long-range haplotype sharing among breeds.</p>
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6.
  • Watson, H. J., et al. (författare)
  • Genome-wide association study identifies eight risk loci and implicates metabo-psychiatric origins for anorexia nervosa
  • 2019
  • Ingår i: Nature Genetics. - 1061-4036. ; 51:8, s. 1207-
  • Tidskriftsartikel (refereegranskat)abstract
    • Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.
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7.
  • Adam, R., et al. (författare)
  • Planck 2015 results IX. Diffuse component separation : CMB maps
  • 2016
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 594
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We present foreground-reduced cosmic microwave background (CMB) maps derived from the full Planck data set in both temperature and polarization. Compared to the corresponding Planck 2013 temperature sky maps, the total data volume is larger by a factor of 3.2 for frequencies between 30 and 70 GHz, and by 1.9 for frequencies between 100 and 857 GHz. In addition, systematic errors in the forms of temperature-topolarization leakage, analogue-to-digital conversion uncertainties, and very long time constant errors have been dramatically reduced, to the extent that the cosmological polarization signal may now be robustly recovered on angular scales l greater than or similar to 40. On the very largest scales, instrumental systematic residuals are still non-negligible compared to the expected cosmological signal, and modes with l &lt; 20 are accordingly suppressed in the current polarization maps by high-pass filtering. As in 2013, four different CMB component separation algorithms are applied to these observations, providing a measure of stability with respect to algorithmic and modelling choices. The resulting polarization maps have rms instrumental noise ranging between 0.21 and 0.27 mu K averaged over 55' pixels, and between 4.5 and 6.1 mu K averaged over 3.'4 pixels. The cosmological parameters derived from the analysis of temperature power spectra are in agreement at the 1 sigma level with the Planck 2015 likelihood. Unresolved mismatches between the noise properties of the data and simulations prevent a satisfactory description of the higher-order statistical properties of the polarization maps. Thus, the primary applications of these polarization maps are those that do not require massive simulations for accurate estimation of uncertainties, for instance estimation of cross-spectra and cross-correlations, or stacking analyses. However, the amplitude of primordial non-Gaussianity is consistent with zero within 2 sigma for all local, equilateral, and orthogonal configurations of the bispectrum, including for polarization E-modes. Moreover, excellent agreement is found regarding the lensing B-mode power spectrum, both internally among the various component separation codes and with the best-fit Planck 2015 Lambda cold dark matter model.</p>
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8.
  • Hou, Liping, et al. (författare)
  • Genome-wide association study of 40,000 individuals identifies two novel loci associated with bipolar disorder.
  • 2016
  • Ingår i: Human molecular genetics. - 1460-2083. ; 25:15, s. 3383-94
  • Tidskriftsartikel (refereegranskat)abstract
    • Bipolar disorder (BD) is a genetically complex mental illness characterized by severe oscillations of mood and behavior. Genome-wide association studies (GWAS) have identified several risk loci that together account for a small portion of the heritability. To identify additional risk loci, we performed a two-stage meta-analysis of >9 million genetic variants in 9,784 bipolar disorder patients and 30,471 controls, the largest GWAS of BD to date. In this study, to increase power we used ∼2,000 lithium-treated cases with a long-term diagnosis of BD from the Consortium on Lithium Genetics, excess controls, and analytic methods optimized for markers on the X-chromosome. In addition to four known loci, results revealed genome-wide significant associations at two novel loci: an intergenic region on 9p21.3 (rs12553324, p = 5.87 × 10(-9); odds ratio = 1.12) and markers within ERBB2 (rs2517959, p = 4.53 × 10(-9); odds ratio = 1.13). No significant X-chromosome associations were detected and X-linked markers explained very little BD heritability. The results add to a growing list of common autosomal variants involved in BD and illustrate the power of comparing well-characterized cases to an excess of controls in GWAS.
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9.
  • Adam, R., et al. (författare)
  • Planck 2015 results X. Diffuse component separation : Foreground maps
  • 2016
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 594
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Planck has mapped the microwave sky in temperature over nine frequency bands between 30 and 857 GHz and in polarization over seven frequency bands between 30 and 353 GHz in polarization. In this paper we consider the problem of diffuse astrophysical component separation, and process these maps within a Bayesian framework to derive an internally consistent set of full-sky astrophysical component maps. Component separation dedicated to cosmic microwave background (CMB) reconstruction is described in a companion paper. For the temperature analysis, we combine the Planck observations with the 9-yr Wilkinson Microwave Anisotropy Probe (WMAP) sky maps and the Haslam et al. 408 MHz map, to derive a joint model of CMB, synchrotron, free-free, spinning dust, CO, line emission in the 94 and 100 GHz channels, and thermal dust emission. Full-sky maps are provided for each component, with an angular resolution varying between 7: 5 and 1 degrees. Global parameters (monopoles, dipoles, relative calibration, and bandpass errors) are fitted jointly with the sky model, and best-fit values are tabulated. For polarization, the model includes CMB, synchrotron, and thermal dust emission. These models provide excellent fits to the observed data, with rms temperature residuals smaller than 4pK over 93% of the sky for all Planck frequencies up to 353 GHz, and fractional errors smaller than 1% in the remaining 7% of the sky. The main limitations of the temperature model at the lower frequencies are internal degeneracies among the spinning dust, free-free, and synchrotron components; additional observations from external low-frequency experiments will be essential to break these degeneracies. The main limitations of the temperature model at the higher frequencies are uncertainties in the 545 and 857 GHz calibration and zero-points. For polarization, the main outstanding issues are instrumental systematics in the 100-353 GHz bands on large angular scales in the form of temperature-to-polarization leakage, uncertainties in the analogue-to-digital conversion, and corrections for the very long time constant of the bolometer detectors, all of which are expected to improve in the near future.</p>
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10.
  • Ade, P. A. R., et al. (författare)
  • Planck 2015 results XX. Constraints on inflation
  • 2016
  • Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 594
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>We present the implications for cosmic inflation of the Planck measurements of the cosmic microwave background (CMB) anisotropies in both temperature and polarization based on the full Planck survey, which includes more than twice the integration time of the nominal survey used for the 2013 release papers. The Planck full mission temperature data and a first release of polarization data on large angular scales measure the spectral index of curvature perturbations to be n(s) = 0.968 +/- 0.006 and tightly constrain its scale dependence to dn(s)/dln k = -0.003 +/- 0.007 when combined with the Planck lensing likelihood. When the Planck high-l polarization data are included, the results are consistent and uncertainties are further reduced. The upper bound on the tensor-to-scalar ratio is r(0).(002) &lt; 0.11 (95% CL). This upper limit is consistent with the B-mode polarization constraint r &lt; 0.12 (95% CL) obtained from a joint analysis of the BICEP2/Keck Array and Planck data. These results imply that V(phi) proportional to phi(2) and natural inflation are now disfavoured compared to models predicting a smaller tensor-to-scalar ratio, such as R-2 inflation. We search for several physically motivated deviations from a simple power-law spectrum of curvature perturbations, including those motivated by a reconstruction of the inflaton potential not relying on the slow-roll approximation. We find that such models are not preferred, either according to a Bayesian model comparison or according to a frequentist simulation-based analysis. Three independent methods reconstructing the primordial power spectrum consistently recover a featureless and smooth P-R (k) over the range of scales 0.008 Mpc(-1) less than or similar to k less than or similar to 0.1 Mpc(-1). At large scales, each method finds deviations from a power law, connected to a deficit at multipoles l approximate to 20-40 in the temperature power spectrum, but at an uncompelling statistical significance owing to the large cosmic variance present at these multipoles. By combining power spectrum and non-Gaussianity bounds, we constrain models with generalized Lagrangians, including Galileon models and axion monodromy models. The Planck data are consistent with adiabatic primordial perturbations, and the estimated values for the parameters of the base Lambda cold dark matter (Lambda CDM) model are not significantly altered when more general initial conditions are admitted. In correlated mixed adiabatic and isocurvature models, the 95% CL upper bound for the non-adiabatic contribution to the observed CMB temperature variance is vertical bar alpha(non-adi)vertical bar &lt; 1.9%, 4.0%, and 2.9% for CDM, neutrino density, and neutrino velocity isocurvature modes, respectively. We have tested inflationary models producing an anisotropic modulation of the primordial curvature power spectrum finding that the dipolar modulation in the CMB temperature field induced by a CDM isocurvature perturbation is not preferred at a statistically significant level. We also establish tight constraints on a possible quadrupolar modulation of the curvature perturbation. These results are consistent with the Planck 2013 analysis based on the nominal mission data and further constrain slow-roll single-field inflationary models, as expected from the increased precision of Planck data using the full set of observations.</p>
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